{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T02:30:50Z","timestamp":1789525850798,"version":"build-2803163510"},"reference-count":90,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T00:00:00Z","timestamp":1740960000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T00:00:00Z","timestamp":1740960000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32473050"],"award-info":[{"award-number":["32473050"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32202829"],"award-info":[{"award-number":["32202829"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32172877"],"award-info":[{"award-number":["32172877"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LQ23C180006"],"award-info":[{"award-number":["LQ23C180006"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"DOI":"10.1038\/s42003-025-07803-8","type":"journal-article","created":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T21:51:01Z","timestamp":1741038661000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Nematode serine protease inhibitor SPI-I8 negatively regulates host NF-\u03baB signalling by hijacking MKRN1-mediated polyubiquitination of RACK1"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4209-7600","authenticated-orcid":false,"given":"Fei","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqiong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueqiu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danni","family":"Tong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingru","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhendong","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2578-6604","authenticated-orcid":false,"given":"Chaoqun","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aifang","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5929-7887","authenticated-orcid":false,"given":"Guangxu","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,3]]},"reference":[{"key":"7803_CR1","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1136\/bjsm.2003.011221","volume":"38","author":"A Scott","year":"2004","unstructured":"Scott, A. et al. What is \u201cinflammation\u201d? Are we ready to move beyond Celsus? Br. J. Sports Med. 38, 248\u2013249 (2004).","journal-title":"Br. J. Sports Med."},{"key":"7803_CR2","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1038\/nature07201","volume":"454","author":"R Medzhitov","year":"2008","unstructured":"Medzhitov, R. Origin and physiological roles of inflammation. Nature 454, 428\u2013435 (2008).","journal-title":"Nature"},{"key":"7803_CR3","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1098\/rstb.2008.0151","volume":"364","author":"G Sorci","year":"2009","unstructured":"Sorci, G. & Faivre, B. Inflammation and oxidative stress in vertebrate host-parasite systems. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 364, 71\u201383 (2009).","journal-title":"Philos. Trans. R. Soc. Lond. B. Biol. Sci."},{"key":"7803_CR4","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1172\/JCI34431","volume":"118","author":"G. M Barton","year":"2008","unstructured":"Barton, G. M. A calculated response: control of inflammation by the innate immune system. J. Clin. Invest. 118, 413\u2013420 (2008).","journal-title":"J. Clin. Invest."},{"key":"7803_CR5","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1016\/j.cell.2010.01.022","volume":"140","author":"O Takeuchi","year":"2010","unstructured":"Takeuchi, O. & Akira, S. Pattern recognition receptors and inflammation. Cell 140, 805\u2013820 (2010).","journal-title":"Cell"},{"key":"7803_CR6","doi-asserted-by":"publisher","first-page":"510","DOI":"10.3382\/ps\/pex314","volume":"97","author":"L. J Broom","year":"2018","unstructured":"Broom, L. J. & Kogut, M. H. Inflammation: friend or foe for animal production? Poult. Sci. 97, 510\u2013514 (2018).","journal-title":"Poult. Sci."},{"key":"7803_CR7","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.it.2022.11.005","volume":"44","author":"M Aqdas","year":"2023","unstructured":"Aqdas, M. & Sung, M. H. NF-\u03baB dynamics in the language of immune cells. Trends Immunol. 44, 32\u201343 (2023).","journal-title":"Trends Immunol."},{"key":"7803_CR8","doi-asserted-by":"publisher","first-page":"S31","DOI":"10.1097\/00005344-199600001-00008","volume":"27","author":"J. H Levy","year":"1996","unstructured":"Levy, J. H. The human inflammatory response. J. Cardiovasc. Pharmacol. 27, S31\u2013S37 (1996).","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"7803_CR9","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1159\/000455857","volume":"9","author":"C. K Lin","year":"2017","unstructured":"Lin, C. K. & Kazmierczak, B. I. Inflammation: a double-edged sword in the response to pseudomonas aeruginosa infection. J. Innate Immun. 9, 250\u2013261 (2017).","journal-title":"J. Innate Immun."},{"key":"7803_CR10","doi-asserted-by":"publisher","first-page":"2471215","DOI":"10.1155\/2019\/2471215","volume":"2019","author":"T Krakauer","year":"2019","unstructured":"Krakauer, T. Inflammasomes, autophagy, and cell death: the trinity of innate host defense against intracellular bacteria. Mediators Inflamm. 2019, 2471215 (2019).","journal-title":"Mediators Inflamm."},{"key":"7803_CR11","doi-asserted-by":"publisher","first-page":"595722","DOI":"10.3389\/fimmu.2021.595722","volume":"12","author":"J. F Rossi","year":"2021","unstructured":"Rossi, J. F. et al. Dynamic immune\/inflammation precision medicine: the good and the bad inflammation in infection and cancer. Front. Immunol. 12, 595722 (2021).","journal-title":"Front. Immunol."},{"key":"7803_CR12","doi-asserted-by":"publisher","first-page":"e18","DOI":"10.1017\/S1462399408000720","volume":"10","author":"W Harnett","year":"2008","unstructured":"Harnett, W. & Harnett, M. M. Therapeutic immunomodulators from nematode parasites. Expert. Rev. Mol. Med. 10, e18 (2008).","journal-title":"Expert. Rev. Mol. Med."},{"key":"7803_CR13","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.pt.2012.02.008","volume":"28","author":"M. J Wolff","year":"2012","unstructured":"Wolff, M. J. et al. Helminthic therapy: improving mucosal barrier function. Trends Parasitol. 28, 187\u2013194 (2012).","journal-title":"Trends Parasitol."},{"key":"7803_CR14","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1016\/S1473-3099(14)70771-6","volume":"14","author":"L. J Wammes","year":"2014","unstructured":"Wammes, L. J. et al. Helminth therapy or elimination: epidemiological, immunological, and clinical considerations. Lancet Infect. Dis. 14, 1150\u20131162 (2014).","journal-title":"Lancet Infect. Dis."},{"key":"7803_CR15","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1016\/j.pt.2019.04.009","volume":"35","author":"K Sobotkov\u00e1","year":"2019","unstructured":"Sobotkov\u00e1, K. et al. Helminth therapy - from the parasite perspective. Trends Parasitol. 35, 501\u2013515 (2019).","journal-title":"Trends Parasitol."},{"key":"7803_CR16","doi-asserted-by":"publisher","DOI":"10.1017\/S0022149X20000802","volume":"94","author":"J Ding","year":"2020","unstructured":"Ding, J. et al. Trichinella spiralis: inflammation modulator. J. Helminthol. 94, e193 (2020).","journal-title":"J. Helminthol."},{"key":"7803_CR17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008508","volume":"16","author":"S. M Ryan","year":"2020","unstructured":"Ryan, S. M. et al. Harnessing helminth-driven immunoregulation in the search for novel therapeutic modalities. PLoS Pathog. 16, e1008508 (2020).","journal-title":"PLoS Pathog."},{"key":"7803_CR18","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1017\/S0031182021001670","volume":"149","author":"V. E Shields","year":"2022","unstructured":"Shields, V. E. & Cooper, J. Use of helminth therapy for management of ulcerative colitis and Crohn\u2019s disease: a systematic review. Parasitology 149, 145\u2013154 (2022).","journal-title":"Parasitology"},{"key":"7803_CR19","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1038\/ni.3772","volume":"18","author":"I. S Afonina","year":"2017","unstructured":"Afonina, I. S. et al. Limiting inflammation-the negative regulation of NF-\u03baB and the NLRP3 inflammasome. Nat. Immunol. 18, 861\u2013869 (2017).","journal-title":"Nat. Immunol."},{"key":"7803_CR20","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1016\/j.celrep.2018.03.097","volume":"23","author":"R Alhallaf","year":"2018","unstructured":"Alhallaf, R. et al. The NLRP3 Inflammasome Suppresses Protective Immunity to Gastrointestinal Helminth Infection. Cell Rep. 23, 1085\u20131098 (2018).","journal-title":"Cell Rep."},{"key":"7803_CR21","doi-asserted-by":"publisher","first-page":"1261","DOI":"10.1124\/mol.62.6.1261","volume":"62","author":"A McCahill","year":"2002","unstructured":"McCahill, A. et al. The RACK1 scaffold protein: a dynamic cog in cell response mechanisms. Mol. Pharmacol. 62, 1261\u20131273 (2002).","journal-title":"Mol. Pharmacol."},{"key":"7803_CR22","doi-asserted-by":"publisher","DOI":"10.1186\/1478-811X-9-22","volume":"9","author":"D. R Adams","year":"2011","unstructured":"Adams, D. R. et al. RACK1, a multifaceted scaffolding protein: structure and function. Cell Commun. Signal. 9, 22 (2011).","journal-title":"Cell Commun. Signal."},{"key":"7803_CR23","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1016\/j.immuni.2014.01.015","volume":"40","author":"L Long","year":"2014","unstructured":"Long, L. et al. Recruitment of phosphatase PP2A by RACK1 adaptor protein deactivates transcription factor IRF3 and limits type I interferon signaling. Immunity 40, 515\u2013529 (2014).","journal-title":"Immunity"},{"key":"7803_CR24","doi-asserted-by":"publisher","first-page":"1280","DOI":"10.1038\/onc.2014.68","volume":"34","author":"T Sato","year":"2015","unstructured":"Sato, T. et al. The TRIM-FLMN protein TRIM45 directly interacts with RACK1 and negatively regulates PKC-mediated signaling pathway. Oncogene 34, 1280\u20131291 (2015).","journal-title":"Oncogene"},{"key":"7803_CR25","doi-asserted-by":"publisher","first-page":"1942","DOI":"10.4049\/jimmunol.1801388","volume":"202","author":"T Murakami","year":"2019","unstructured":"Murakami, T. et al. Cutting edge: G protein subunit \u03b2 1 negatively regulates nlrp3 inflammasome activation. J. Immunol. 202, 1942\u20131947 (2019).","journal-title":"J. Immunol."},{"key":"7803_CR26","doi-asserted-by":"publisher","first-page":"108711","DOI":"10.1016\/j.vetmic.2020.108711","volume":"246","author":"X Wang","year":"2020","unstructured":"Wang, X. et al. Porcine RACK1 negatively regulates the infection of classical swine fever virus and the NF-\u03baB activation in PK-15 cells. Vet. Microbiol. 246, 108711 (2020).","journal-title":"Vet. Microbiol."},{"key":"7803_CR27","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1038\/cr.2013.162","volume":"24","author":"F Yao","year":"2014","unstructured":"Yao, F. et al. RACK1 modulates NF-\u03baB activation by interfering with the interaction between TRAF2 and the IKK complex. Cell Res. 24, 359\u2013371 (2014).","journal-title":"Cell Res."},{"key":"7803_CR28","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1038\/365797a0","volume":"365","author":"R. M Maizels","year":"1993","unstructured":"Maizels, R. M. et al. Immunological modulation and evasion by helminth parasites in human populations. Nature 365, 797\u2013805 (1993).","journal-title":"Nature"},{"key":"7803_CR29","doi-asserted-by":"publisher","first-page":"1291","DOI":"10.1016\/S0020-7519(03)00163-2","volume":"33","author":"S Hartmann","year":"2003","unstructured":"Hartmann, S. & Lucius, R. Modulation of host immune responses by nematode cystatins. Int. J. Parasitol. 33, 1291\u20131302 (2003).","journal-title":"Int. J. Parasitol."},{"key":"7803_CR30","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1016\/j.immuni.2018.10.016","volume":"49","author":"R. M Maizels","year":"2018","unstructured":"Maizels, R. M. et al. Modulation of host immunity by helminths: the expanding repertoire of parasite effector molecules. Immunity 49, 801\u2013818 (2018).","journal-title":"Immunity"},{"key":"7803_CR31","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2202795119","volume":"119","author":"S. M Ryan","year":"2022","unstructured":"Ryan, S. M. et al. Novel antiinflammatory biologics shaped by parasite-host coevolution. Proc. Natl. Acad. Sci. USA 119, e2202795119 (2022).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"7803_CR32","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6488","volume":"5","author":"A. H Buck","year":"2014","unstructured":"Buck, A. H. et al. Exosomes secreted by nematode parasites transfer small RNAs to mammalian cells and modulate innate immunity. Nat. Commun. 5, 5488 (2014).","journal-title":"Nat. Commun."},{"key":"7803_CR33","doi-asserted-by":"publisher","DOI":"10.1038\/cti.2017.42","volume":"6","author":"I. B Ferreira","year":"2017","unstructured":"Ferreira, I. B. et al. Suppression of inflammation and tissue damage by a hookworm recombinant protein in experimental colitis. Clin. Transl. Immunol. 6, e157 (2017).","journal-title":"Clin. Transl. Immunol."},{"key":"7803_CR34","doi-asserted-by":"publisher","first-page":"850","DOI":"10.3389\/fimmu.2018.00850","volume":"9","author":"R. M Eichenberger","year":"2018","unstructured":"Eichenberger, R. M. et al. Hookworm secreted extracellular vesicles interact with host cells and prevent inducible colitis in mice. Front. Immunol. 9, 850 (2018).","journal-title":"Front. Immunol."},{"key":"7803_CR35","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.trsl.2021.02.012","volume":"232","author":"G Buitrago","year":"2021","unstructured":"Buitrago, G. et al. A netrin domain-containing protein secreted by the human hookworm Necator americanus protects against CD4 T cell transfer colitis. Transl. Res. 232, 88\u2013102 (2021).","journal-title":"Transl. Res."},{"key":"7803_CR36","doi-asserted-by":"publisher","first-page":"781108","DOI":"10.3389\/fimmu.2021.781108","volume":"12","author":"K. A Hildersley","year":"2021","unstructured":"Hildersley, K. A. et al. Tuft cells increase following ovine intestinal parasite infections and define evolutionarily conserved and divergent responses. Front. Immunol. 12, 781108 (2021).","journal-title":"Front. Immunol."},{"key":"7803_CR37","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jbiotec.2021.08.006","volume":"340","author":"D. J Smyth","year":"2021","unstructured":"Smyth, D. J. et al. Oral delivery of a functional algal-expressed TGF-\u03b2 mimic halts colitis in a murine DSS model. J. Biotechnol. 340, 1\u201312 (2021).","journal-title":"J. Biotechnol."},{"key":"7803_CR38","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1016\/j.ijpara.2021.11.001","volume":"51","author":"A Loukas","year":"2021","unstructured":"Loukas, A. et al. The yin and yang of human soil-transmitted helminth infections. Int. J. Parasitol. 51, 1243\u20131253 (2021).","journal-title":"Int. J. Parasitol."},{"key":"7803_CR39","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20211140","volume":"219","author":"C Drurey","year":"2022","unstructured":"Drurey, C. et al. Intestinal epithelial tuft cell induction is negated by a murine helminth and its secreted products. J. Exp. Med. 219, e20211140 (2022).","journal-title":"J. Exp. Med."},{"key":"7803_CR40","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1016\/j.ijpara.2021.05.002","volume":"51","author":"F Wu","year":"2021","unstructured":"Wu, F. et al. The trypsin inhibitor-like domain is required for a serine protease inhibitor of Haemonchus contortus to inhibit host coagulation. Int. J. Parasitol. 51, 1015\u20131026 (2021).","journal-title":"Int. J. Parasitol."},{"key":"7803_CR41","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2013-14-8-r88","volume":"14","author":"R Laing","year":"2013","unstructured":"Laing, R. et al. The genome and transcriptome of Haemonchus contortus, a key model parasite for drug and vaccine discovery. Genome Biol. 14, R88 (2013).","journal-title":"Genome Biol."},{"key":"7803_CR42","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2013-14-8-r89","volume":"14","author":"E. M Schwarz","year":"2013","unstructured":"Schwarz, E. M. et al. The genome and developmental transcriptome of the strongylid nematode Haemonchus contortus. Genome Biol. 14, R89 (2013).","journal-title":"Genome Biol."},{"key":"7803_CR43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.apar.2016.02.021","volume":"93","author":"R. B Gasser","year":"2016","unstructured":"Gasser, R. B. & von Samson-Himmelstjerna, G. Haemonchus contortus and Haemonchosis\u2014Past, Present and Future Trends. Adv. Parasitol. 93, 1\u2013666 (2016).","journal-title":"Adv. Parasitol."},{"key":"7803_CR44","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1038\/s41588-018-0262-1","volume":"51","author":"International Helminth Genomes Consortium","year":"2019","unstructured":"International Helminth Genomes Consortium Comparative genomics of the major parasitic worms. Nat. Genet. 51, 163\u2013174 (2019).","journal-title":"Nat. Genet."},{"key":"7803_CR45","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.pt.2018.09.010","volume":"35","author":"A. R Jex","year":"2019","unstructured":"Jex, A. R., Gasser, R. B. & Schwarz, E. M. Transcriptomic resources for parasitic nematodes of veterinary importance. Trends Parasitol. 35, 72\u201384 (2019).","journal-title":"Trends Parasitol."},{"key":"7803_CR46","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1038\/s42003-020-01377-3","volume":"3","author":"S. R Doyle","year":"2020","unstructured":"Doyle, S. R. et al. Genomic and transcriptomic variation defines the chromosome-scale assembly of Haemonchus contortus, a model gastrointestinal worm. Commun. Biol. 3, 656 (2020).","journal-title":"Commun. Biol."},{"key":"7803_CR47","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2019.05.003","volume":"204","author":"T Wang","year":"2019","unstructured":"Wang, T. et al. High throughput LC-MS\/MS-based proteomic analysis of excretory-secretory products from short-term in vitro culture of Haemonchus contortus. J. Proteom. 204, 103375 (2019).","journal-title":"J. Proteom."},{"key":"7803_CR48","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/S0968-0004(99)01384-5","volume":"24","author":"T. F Smith","year":"1999","unstructured":"Smith, T. F. et al. The WD repeat: a common architecture for diverse functions. Trends Biochem. Sci. 24, 181\u2013185 (1999).","journal-title":"Trends Biochem. Sci."},{"key":"7803_CR49","doi-asserted-by":"publisher","first-page":"20263","DOI":"10.1074\/jbc.M109.017640","volume":"284","author":"P. A Kiely","year":"2009","unstructured":"Kiely, P. A. et al. Phosphorylation of RACK1 on tyrosine 52 by c-Abl is required for insulin-like growth factor I-mediated regulation of focal adhesion kinase. J. Biol. Chem. 284, 20263\u201320274 (2009).","journal-title":"J. Biol. Chem."},{"key":"7803_CR50","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1016\/j.cellsig.2017.01.026","volume":"35","author":"M. H Nielsen","year":"2017","unstructured":"Nielsen, M. H. et al. Structural analysis of ribosomal RACK1 and its role in translational control. Cell. Signal. 35, 272\u2013281 (2017).","journal-title":"Cell. Signal."},{"key":"7803_CR51","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1006\/geno.2000.6199","volume":"66","author":"T. A Gray","year":"2000","unstructured":"Gray, T. A. et al. The ancient source of a distinct gene family encoding proteins featuring RING and C(3)H zinc-finger motifs with abundant expression in developing brain and nervous system. Genomics 66, 76\u201386 (2000).","journal-title":"Genomics"},{"key":"7803_CR52","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-11-721","volume":"11","author":"A B\u00f6hne","year":"2010","unstructured":"B\u00f6hne, A. et al. The vertebrate makorin ubiquitin ligase gene family has been shaped by largescale duplication and retroposition from an ancestral gonad-specific, maternal-effect gene. BMC Genomics 11, 721 (2010).","journal-title":"BMC Genomics"},{"key":"7803_CR53","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1055\/s-0039-3400965","volume":"37","author":"L Naul\u00e9","year":"2019","unstructured":"Naul\u00e9, L. & Kaiser, U. B. Evolutionary conservation of MKRN3 and other makorins and their roles in puberty initiation and endocrine functions. Semin. Reprod. Med. 37, 166\u2013173 (2019).","journal-title":"Semin. Reprod. Med."},{"key":"7803_CR54","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1101\/gad.1289405","volume":"19","author":"J. H Kim","year":"2005","unstructured":"Kim, J. H. et al. Ubiquitin ligase MKRN1 modulates telomere length homeostasis through a proteolysis of hTERT. Genes Dev. 19, 776\u2013781 (2005).","journal-title":"Genes Dev."},{"key":"7803_CR55","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms1981","volume":"3","author":"E. W Lee","year":"2012","unstructured":"Lee, E. W. et al. Ubiquitination and degradation of the FADD adaptor protein regulate death receptor-mediated apoptosis and necroptosis. Nat. Commun. 3, 978 (2012).","journal-title":"Nat. Commun."},{"key":"7803_CR56","doi-asserted-by":"publisher","first-page":"10599","DOI":"10.1073\/pnas.92.23.10599","volume":"92","author":"I Alkalay","year":"1995","unstructured":"Alkalay, I. et al. Stimulation-dependent I kappa B alpha phosphorylation marks the NF-kappaB inhibitor for degradation via the ubiquitin-proteasome pathway. Proc. Natl. Acad. Sci. USA 92, 10599\u201310603 (1995).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"7803_CR57","doi-asserted-by":"publisher","first-page":"1586","DOI":"10.1101\/gad.9.13.1586","volume":"9","author":"Z Chen","year":"1995","unstructured":"Chen, Z. et al. Signal-induced site-specific phosphorylation targets I kappa B alpha to the ubiquitin-proteasome pathway. Genes Dev. 9, 1586\u20131597 (1995).","journal-title":"Genes Dev."},{"key":"7803_CR58","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/ni0102-20","volume":"3","author":"Y Ben-Neriah","year":"2002","unstructured":"Ben-Neriah, Y. Regulatory functions of ubiquitination in the immune system. Nat. Immunol. 3, 20\u201326 (2002).","journal-title":"Nat. Immunol."},{"key":"7803_CR59","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1038\/sj.embor.7400380","volume":"6","author":"D Krappmann","year":"2005","unstructured":"Krappmann, D. & Scheidereit, C. A pervasive role of ubiquitin conjugation in activation and termination of I kappa B kinase pathways. EMBO Rep. 6, 321\u2013326 (2005).","journal-title":"EMBO Rep."},{"key":"7803_CR60","doi-asserted-by":"publisher","first-page":"S123","DOI":"10.1017\/S0031182000086017","volume":"96","author":"M. W Lightowlers","year":"1988","unstructured":"Lightowlers, M. W. & Rickard, M. D. Excretory-secretory products of helminth parasites: effects on host immune responses. Parasitology 96, S123\u2013S166 (1988).","journal-title":"Parasitology"},{"key":"7803_CR61","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1038\/nri1183","volume":"3","author":"R. M Maizels","year":"2003","unstructured":"Maizels, R. M. & Yazdanbakhsh, M. Immune regulation by helminth parasites: cellular and molecular mechanisms. Nat. Rev. Immunol. 3, 733\u2013744 (2003).","journal-title":"Nat. Rev. Immunol."},{"key":"7803_CR62","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/j.molbiopara.2014.03.007","volume":"195","author":"W Harnett","year":"2014","unstructured":"Harnett, W. Secretory products of helminth parasites as immunomodulators. Mol. Biochem. Parasitol. 195, 130\u2013136 (2014).","journal-title":"Mol. Biochem. Parasitol."},{"key":"7803_CR63","doi-asserted-by":"publisher","first-page":"577846","DOI":"10.3389\/fmicb.2020.577846","volume":"11","author":"S. D Bobardt","year":"2020","unstructured":"Bobardt, S. D. et al. The two faces of nematode infection: virulence and immunomodulatory molecules from nematode parasites of mammals, insects and plants. Front. Microbiol. 11, 577846 (2020).","journal-title":"Front. Microbiol."},{"key":"7803_CR64","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1645\/21-33","volume":"108","author":"O. K Okakpu","year":"2022","unstructured":"Okakpu, O. K. & Dillman, A. R. Review of the role of parasitic nematode excretory\/secretory proteins in host immunomodulation. J. Parasitol. 108, 199\u2013208 (2022).","journal-title":"J. Parasitol."},{"key":"7803_CR65","doi-asserted-by":"publisher","first-page":"1493","DOI":"10.1016\/S0140-6736(01)06579-5","volume":"358","author":"S Scrivener","year":"2001","unstructured":"Scrivener, S. et al. Independent effects of intestinal parasite infection and domestic allergen exposure on risk of wheeze in Ethiopia: a nested case-control study. Lancet 358, 1493\u20131499 (2001).","journal-title":"Lancet"},{"key":"7803_CR66","doi-asserted-by":"publisher","first-page":"2034","DOI":"10.1111\/j.1572-0241.2003.07660.x","volume":"98","author":"R. W Summers","year":"2003","unstructured":"Summers, R. W. et al. Trichuris suis seems to be safe and possibly effective in the treatment of inflammatory bowel disease. Am. J. Gastroenterol. 98, 2034\u20132041 (2003).","journal-title":"Am. J. Gastroenterol."},{"key":"7803_CR67","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1136\/gut.2004.041749","volume":"54","author":"R. W Summers","year":"2005","unstructured":"Summers, R. W. et al. Trichuris suis therapy in Crohn\u2019s disease. Gut 54, 87\u201390 (2005).","journal-title":"Gut"},{"key":"7803_CR68","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1136\/gut.2005.079129","volume":"55","author":"J Croese","year":"2006","unstructured":"Croese, J. et al. A proof of concept study establishing Necator americanus in Crohn\u2019s patients and reservoir donors. Gut 55, 136\u2013137 (2006).","journal-title":"Gut"},{"key":"7803_CR69","doi-asserted-by":"publisher","first-page":"1305","DOI":"10.1016\/j.jaci.2006.08.035","volume":"118","author":"C Flohr","year":"2006","unstructured":"Flohr, C. et al. Poor sanitation and helminth infection protect against skin sensitization in Vietnamese children: a cross-sectional study. J. Allergy Clin. Immunol. 118, 1305\u20131311 (2006).","journal-title":"J. Allergy Clin. Immunol."},{"key":"7803_CR70","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.jaci.2009.08.006","volume":"125","author":"P Bager","year":"2010","unstructured":"Bager, P. et al. Trichuris suis ova therapy for allergic rhinitis: a randomized, double-blind, placebo-controlled clinical trial. J. Allergy Clin. Immunol. 125, 123\u2013130 (2010).","journal-title":"J. Allergy Clin. Immunol."},{"key":"7803_CR71","doi-asserted-by":"publisher","first-page":"4721","DOI":"10.4049\/jimmunol.179.7.4721","volume":"179","author":"M Weng","year":"2007","unstructured":"Weng, M. et al. Alternatively activated macrophages in intestinal helminth infection: effects on concurrent bacterial colitis. J. Immunol. 179, 4721\u20134731 (2007).","journal-title":"J. Immunol."},{"key":"7803_CR72","doi-asserted-by":"publisher","first-page":"1068","DOI":"10.1038\/mi.2013.123","volume":"7","author":"H. J McSorley","year":"2014","unstructured":"McSorley, H. J. et al. Blockade of IL-33 release and suppression of type 2 innate lymphoid cell responses by helminth secreted products in airway allergy. Mucosal. Immunol. 7, 1068\u20131078 (2014).","journal-title":"Mucosal. Immunol."},{"key":"7803_CR73","doi-asserted-by":"publisher","first-page":"1834","DOI":"10.3389\/fmicb.2017.01834","volume":"8","author":"N Xu","year":"2017","unstructured":"Xu, N. et al. Recombinant trichinella pseudospiralis serine protease inhibitors alter macrophage polarization in vitro. Front. Microbiol. 8, 1834 (2017).","journal-title":"Front. Microbiol."},{"key":"7803_CR74","doi-asserted-by":"publisher","first-page":"963","DOI":"10.4049\/jimmunol.2000290","volume":"206","author":"N Xu","year":"2021","unstructured":"Xu, N. et al. The anti-inflammatory immune response in early Trichinella spiralis intestinal infection depends on serine protease inhibitor-mediated alternative activation of macrophages. J. Immunol. 206, 963\u2013977 (2021).","journal-title":"J. Immunol."},{"key":"7803_CR75","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/S0968-0004(00)01761-8","volume":"26","author":"X Zang","year":"2001","unstructured":"Zang, X. & Maizels, R. M. Serine proteinase inhibitors from nematodes and the arms race between host and pathogen. Trends Biochem. Sci. 26, 191\u2013197 (2001).","journal-title":"Trends Biochem. Sci."},{"key":"7803_CR76","doi-asserted-by":"publisher","first-page":"2427","DOI":"10.1007\/s00018-003-3120-x","volume":"60","author":"D Krowarsch","year":"2003","unstructured":"Krowarsch, D. et al. Canonical protein inhibitors of serine proteases. Cell. Mol. Life Sci. 60, 2427\u20132444 (2003).","journal-title":"Cell. Mol. Life Sci."},{"key":"7803_CR77","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1038\/nature16527","volume":"529","author":"F Gerbe","year":"2016","unstructured":"Gerbe, F. et al. Intestinal epithelial tuft cells initiate type 2 mucosal immunity to helminth parasites. Nature 529, 226\u2013230 (2016).","journal-title":"Nature"},{"key":"7803_CR78","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1016\/j.molmed.2016.09.005","volume":"22","author":"S. P Steele","year":"2016","unstructured":"Steele, S. P. et al. Tuft cells: new players in colitis. Trends Mol. Med. 22, 921\u2013924 (2016).","journal-title":"Trends Mol. Med."},{"key":"7803_CR79","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1038\/nature16161","volume":"529","author":"J von Moltke","year":"2016","unstructured":"von Moltke, J. et al. Tuft-cell-derived IL-25 regulates an intestinal ILC2-epithelial response circuit. Nature 529, 221\u2013225 (2016).","journal-title":"Nature"},{"key":"7803_CR80","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1038\/s41586-021-03828-1","volume":"596","author":"K Tunyasuvunakool","year":"2021","unstructured":"Tunyasuvunakool, K. et al. Highly accurate protein structure prediction for the human proteome. Nature 596, 590\u2013596 (2021).","journal-title":"Nature"},{"key":"7803_CR81","doi-asserted-by":"publisher","first-page":"D439","DOI":"10.1093\/nar\/gkab1061","volume":"50","author":"M Varadi","year":"2022","unstructured":"Varadi, M. et al. AlphaFold protein structure database: massively expanding the structural coverage of protein-sequence space with high-accuracy models. Nucleic Acids Res. 50, D439\u2013D444 (2022).","journal-title":"Nucleic Acids Res."},{"key":"7803_CR82","doi-asserted-by":"publisher","first-page":"W96","DOI":"10.1093\/nar\/gkh354","volume":"32","author":"S. R Comeau","year":"2004","unstructured":"Comeau, S. R. et al. ClusPro: a fully automated algorithm for protein\u2013protein docking. Nucleic Acids Res. 32, W96\u2013W99 (2004).","journal-title":"Nucleic Acids Res."},{"key":"7803_CR83","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1038\/nprot.2016.169","volume":"12","author":"D Kozakov","year":"2017","unstructured":"Kozakov, D. et al. The ClusPro web server for protein\u2013 protein docking. Nat. Protoc. 12, 255\u2013278 (2017).","journal-title":"Nat. Protoc."},{"key":"7803_CR84","doi-asserted-by":"publisher","first-page":"W322","DOI":"10.1093\/nar\/gkz397","volume":"47","author":"G. Q Weng","year":"2019","unstructured":"Weng, G. Q. et al. HawkDock: a web server to predict and analyze the structures of protein-protein complexes based on computational docking and MM\/GBSA. Nucleic Acids Res. 47, W322\u2013W330 (2019).","journal-title":"Nucleic Acids Res."},{"key":"7803_CR85","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1002\/pro.3235","volume":"27","author":"T. D Goddard","year":"2018","unstructured":"Goddard, T. D. et al. UCSF chimeraX: meeting modern challenges in visualization and analysis. Protein Sci. 27, 14\u201325 (2018).","journal-title":"Protein Sci."},{"key":"7803_CR86","first-page":"273","volume":"2018","author":"M Sena-Esteves","year":"2018","unstructured":"Sena-Esteves, M. & Gao, G. Production of high-titer retrovirus and lentivirus vectors. Cold Spring Harb. Protoc. 2018, 273\u2013280 (2018).","journal-title":"Cold Spring Harb. Protoc."},{"key":"7803_CR87","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1016\/j.cell.2018.03.064","volume":"173","author":"M Jiang","year":"2018","unstructured":"Jiang, M. et al. Self-recognition of an inducible host lncRNA by RIG-I feedback restricts innate immune response. Cell 173, 906\u2013919.e13 (2018).","journal-title":"Cell"},{"key":"7803_CR88","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.1016\/j.cell.2006.01.040","volume":"124","author":"J Moffat","year":"2006","unstructured":"Moffat, J. et al. A lentiviral RNAi library for human and mouse genes applied to an arrayed viral high-content screen. Cell 124, 1283\u20131298 (2006).","journal-title":"Cell"},{"key":"7803_CR89","doi-asserted-by":"publisher","first-page":"4557","DOI":"10.4049\/jimmunol.178.7.4557","volume":"178","author":"P Smith","year":"2007","unstructured":"Smith, P. et al. Infection with a helminth parasite prevents experimental colitis via a macrophage-mediated mechanism. J. Immunol. 178, 4557\u20134566 (2007).","journal-title":"J. Immunol."},{"key":"7803_CR90","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21940-8","volume":"12","author":"S Bang","year":"2021","unstructured":"Bang, S. et al. Activation of GPR37 in macrophages confers protection against infection-induced sepsis and pain-like behaviour in mice. Nat. Commun. 12, 1704 (2021).","journal-title":"Nat. Commun."}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-07803-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-07803-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-07803-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T09:30:20Z","timestamp":1741080620000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-07803-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,3]]},"references-count":90,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["7803"],"URL":"https:\/\/doi.org\/10.1038\/s42003-025-07803-8","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,3]]},"assertion":[{"value":"25 August 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 February 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 March 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"356"}}